Lung has been shown to perform important non-respiratory functions, among which are the removal and metabolism of circulating biogenic amines and drugs. Since impairment of this capacity by environmental agents could contribute to their toxicity, the effects of selected environmental toxins on pulmonary drug clearance will be examined. Since carbon monoxide and nicotine are known to cause cardiovascular changes, isolated lungs from rats pretreated with these agents will be tested for their ability to clear circulating vasoactive biogenic amines (5-hydroxytryptamine and norepinephrine) as well as selected drugs (propranolol, methadone). Paraquat produces severe lung lesions in animals and humans; therefore, the influence of this herbicide on pulmonary clearance of biogenic amines and drugs will also be examined. Studies of metabolism in broken-cell preparations have led many to believe that drug clearance by lung in vivo is minor compared to that of liver. Therefore, clearance of selected drugs and vasoactive biogenic amines will be compared in intact liver and lung at physiological perfusion rates in order to assess the relative contribution of these organs in vivo. In addition, relative metabolic clearance by intact lung and liver will be compared with relative metabolic rates in broken-cell preparations.